Ran is an evolutionary conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Ran Binding Protein 1 (RanBP1) has guanine nucleotide dissociation inhibitory activity, specific for the GTP form of Ran and also functions to stimulate Ran GTPase activating protein(GAP)-mediated GTP hydrolysis by Ran. RanBP1 contributes to maintaining the gradient of RanGTP across the nuclear envelope high (GDI activity) or the cytoplasmic levels of RanGTP low (GAP cofactor) [(PUBMED:12019565)].

All RanBP1 proteins contain an approx 150 amino acid residue Ran binding domain. Ran BP1 binds directly to RanGTP with high affinity. There are four sites of contact between Ran and the Ran binding domain. One of these involves binding of the C-terminal segment of Ran to a groove on the Ran binding domain that is analogous to the surface utilised in the EVH1-peptide interaction [(PUBMED:10404224)]. Nup358 contains four Ran binding domains. The structure of the first of these is known [(PUBMED:10078529)].

EVH1/WH1 domains of VASP and WASP proteins belong to a large family including Ran-binding domains of the RanBP1 family.

FEBS Lett. 1998; 441: 181-5

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The two cytoskeletal proteins VASP and WASP and the protein Homer share a conserved domain, currently designated the WHI domain (WASP homology domain 1) or EVH1 domain (ENA/VASP homology domain 1), which could play an important role in various cellular events such as transport, folding of proteins, and signal transduction. We report here additional occurrences of this domain in Ran-binding proteins of the RanBP1 family and various others proteins, or putative proteins of eukaryotic organisms, suggesting that the EVH1/WH1 domain may be more widely used than originally thought.

The Ran/TC4 GTPase-binding domain: identification by expression cloning and characterization of a conserved sequence motif.

Proc Natl Acad Sci U S A. 1995; 92: 3328-32

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Ran/TC4 is an essential, nuclear GTPase implicated in the initiation of DNA replication, entry into and exit from mitosis, and in nuclear RNA and protein transport through the nuclear pore complex. This diversity of functions suggests that Ran interacts with a large number of down-stream targets. Using an overlay assay, we detected a family of putative target proteins that associate with GTP-bound Ran. The sequence of only one such protein, HTF9a/RanBP1, is known. We have now cloned two additional Ran-binding proteins, allowing identification of a distinctive, highly conserved sequence motif of approximately 150 residues. This motif represents a minimal Ran-binding domain that stabilizes the GTP-bound state of Ran. The isolated domain also functions as a coactivator of Ran-GTPase-activating protein. Mutation of a conserved residue within the Ran-binding domain of HTF9a protein drastically reduced Ran binding. Ran-binding proteins coimmunoprecipitated with epitope-tagged Ran from cell lysates, suggesting that these proteins may associate in vivo. A previously uncharacterized Caenorhabditis elegans gene could encode a protein (96 kDa) possessing two Ran-binding domains. This open reading frame also contains similarities to nucleoporins, suggesting a functional link between Ran and nuclear pore complexes.

Ran, a small nuclear GTP binding protein, is essential for the translocation of nuclear proteins through the nuclear pore complex. We show that several proteins, including the Saccharomyces cerevisiae Nup2p and Caenorhabditis elegans F59A2.1 nucleoporins, contain domains similar to the previously characterized murine Ran binding protein (RBP, termed RBP1). To test the significance of this similarity, we have used the corresponding domains of Nup2p and a putative S. cerevisiae RBP in Ran binding assays and the yeast two-hybrid system. Both proteins bind S. cerevisiae Ran, but only the putative S. cerevisiae RBP binds human Ran. Two-hybrid analysis revealed Ran-Ran interactions and that yeast and human Rans can interact. These data identify Nup2p as a target for Ran in the nuclear pore complex, suggesting a direct role for it in nuclear-cytoplasmic transport. We discuss the possibility that proteins harboring Ran binding domains link the Ran GTPase cycle to specific functions in the nucleus.

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with RanBD domain which could be assigned to a KEGG orthologous group, and not all proteins containing RanBD domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.